Serum Leptin Levels Positively Correlate With Peripheral Arterial Stiffness in Kidney Transplantation Patients M.-C. Lee, Y.-C. Chen, G.-J. Ho, M.-H. Shih, K.-C. Chou, and B.-G. Hsu ABSTRACT Background. Leptin is a protein predominantly produced by adipocytes that plays a pathophysiologic role in the pathogenesis of hypertension and cardiovascular diseases. The aim of this study was to evaluate the relationship between fasting serum leptin levels and peripheral arterial stiffness among kidney transplant (KT) patients. Methods. Fasting blood samples were obtained from 74 KT patients. Brachial-ankle pulse wave velocity (baPWV) was measured in the right or left brachial artery to the ankle segments using an automatic pulse wave analyzer (VaSera VS-1000). Plasma leptin levels were measured using a commercial enzyme-linked immunosorbent assay kit. In this study, left or right baPWV values of less than 14.0 m/s were used to define the high arterial stiffness group. Results. Forty KT patients (54.1%) were defined in high arterial stiffness group. Hypertension (P < .010), diabetes (P < .010), age (P ¼ .010), KT duration (P ¼ .013), triglyceride levels (P ¼ .016), systolic blood pressure (P < .001), waist circumference (P ¼ .031), and leptin level (P < .001) were higher, whereas serum high-density lipoprotein cholesterol level (P ¼ .030) was lower in the high arterial stiffness group compared with the low arterial stiffness group. Multivariate logistic regression analysis showed that leptin (odds ratio, 1.033; 95% CI, 1.004e1.062; P ¼ .023), KT duration (odds ratio, 1.023; 95% CI, 1.004e1.044; P ¼ .020), and high-density lipoprotein cholesterol level (odds ratio, 0.925; 95% CI, 0.872e0.982; P ¼ .010) were the independent predictors of peripheral arterial stiffness in KT patients. Conclusions. Serum fasting leptin level was positively associated with peripheral arterial stiffness among KT patients.
C
ARDIOVASCULAR DISEASE remains a major cause of mortality in kidney transplant (KT) patients, which is partially attributed to nonclassic cardiovascular risk factors, including arterial stiffness [1,2]. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in KT patients [3]. Pulse wave velocity (PWV) measurement is one of the noninvasive methods that are currently used to assess vascular dysfunction [4]. A close correlation between brachial-ankle PWV (baPWV) and carotid-femoral PWV has been reported [5]. Leptin is almost exclusively secreted by white and brown adipocytes [6]. Leptin plays a pathophysiologic role in the pathogenesis of hypertension and cardiovascular diseases [7]. Leptin may contribute to the development of arterial hypertension mainly through increased sympathetic nervous activity, and the development of endothelial dysfunction ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 353e358 (2014)
through the regulation of blood vessel tonus and imbalance between endothelial nitric oxide synthase expression and intracellular L-arginine [8,9]. Leptin may participate in the pathogenesis of atherogenesis through the stimulation of platelet aggregation, inflammation, endothelial dysfunction,
From the School of Medicine, Tzu Chi University (M.-C.L., B.G.H.), and the Departments of Surgery (M.-C.L., Y.-C.C., G.-J.H.), Nursing (M.-H.S., K.-C.C.), and Nephrology (B.-G.H.), Buddhist Tzu Chi General Hospital, Hualien, Taiwan. Supported by a grant from Buddhist Tzu Chi General Hospital, Hualien, Taiwan (TCRD101-06). Address reprint requests to Bang-Gee Hsu, Division of Nephrology, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Chung Yang Road, 97004 Hualien, Taiwan. E-mail: gee.lily@ msa.hinet.net 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.145 353
354
neointimal hyperplasia, neutrophil chemotaxis, and vascular smooth muscle cell proliferation and migration [7,10]. Leptin is independent correlates of carotid-femoral PWV in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging [11]. The aim of the present study was to determine the relationship between serum leptin concentrations and peripheral arterial stiffness among KT patients. PATIENTS AND METHODS Patients Seventy-four KT patients were studied in April 2010 in a medical center in Hualien, Taiwan, including 40 males and 34 females with ages ranging from 27 to 75 years. The study was approved by the Protection of Human Subjects Institutional Review Board of TzuChi University and Hospital. Patients were excluded if they had any acute infection, malignancy, acute rejection, acute myocardial infarction, pulmonary edema, heart failure at the time of blood sampling, an arterial-venous shunt or graft in the hands, or if they refused to provide informed consent for the study.
Anthropometric Analysis Body weight was measured to the nearest half kilogram with the patient in light clothing and without shoes. Height was measured to the nearest half centimeter, and waist circumference was measured to the nearest half centimeter at the shortest point below the lower rib margin and the iliac crest. Body mass index was calculated as weight (kilograms) divided by height squared (meters) [12e14].
Biochemical Determinations Fasting blood samples of approximately 5 m1 for measuring complete blood cell count (Sysmex K-1000, Sysmex, Bohemia, NY) and other factors were immediately centrifuged at 3000 g for 10 minutes after collection. Serum samples were stored at 4 C and used for biochemical analyses within 1 hour of collection. Serum levels of blood urea nitrogen, creatinine, fasting glucose, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol, total calcium, and phosphorus were measured using an autoanalyzer (COBAS Integra 800, Roche Diagnostics, Basel, Switzerland). Serum leptin (SPI-BIO, Montigny le Bretonneux, France) concentrations were determined using a commercially available enzyme immunoassay [12,13]. The minimum detectable concentration of human leptin dose was determined by adding 2 standard deviations to the mean optical density value of twenty zero standards replicates and calculating the corresponding concentration was 7.8 pg/mL. The inter- and intra-assay coefficients of variation for leptin were 4.2% and 3.0%. Serum intact parathyroid hormone (Diagnostic Systems Laboratories, Webster, TX) levels were measured using a commercially available enzyme-linked immunosorbent assays [12e14].
Blood Pressure and baPWV Measurements After blood sampling, baPWV measurements were taken the same day. Measurements were performed in a quiet, temperaturecontrolled room after 10 minutes at rest, with the patients in a supine position according to the recommendations for user procedures of clinical applications of arterial stiffness. Blood pressure and heart rate (mean of 3 readings) were measured with an automatic upper arm oscillometric device. Pulse pressure was calculated
LEE, CHEN, HO ET AL by subtracting diastolic (DBP) from systolic blood pressure (SBP). The baPWV was measured in the right or left brachial artery to the ankle segments using an automatic pulse wave analyzer (VaSera VS-1000, Fukuda Denshi Co. Ltd., Tokyo, Japan). In brief, cuffs were applied to the 4 extremities and electrocardiographic electrodes were attached to the upper arm. A microphone was placed on the sternal angle for phonocardiography. The subjects then rested in a supine position for 5 minutes. The baPWV was calculated by dividing the distance from the aortic valve to the ankle artery by the sum of the difference between the time the pulse waves were transmitted to the brachium and the time the same waves were transmitted to the ankle, and the time difference between the second heart sound on the phonocardiogram and the notch of the brachial pulse wave. To minimize cuff inflation effects on blood flow dynamics, pulse waves were measured with the cuffs inflated to less than the DBP (50 mmHg). The extremity blood pressure was then measured by oscillometry. SBP and DBP were obtained by measuring the blood pressure at the right brachial artery [15]. In this study, left or right baPWV values of less than 14.0 m/s were used to define the high arterial stiffness group [15].
Statistical Analysis Data were expressed as mean values standard deviation (SD) and were tested for normal distribution using the KolmogoroveSmirnov test. Comparisons between patients were performed using the Student’s independent t test (2-tailed) for normally distributed data, or the Mann-Whitney U test for parameters that presented with non-normal distribution (TG, fasting glucose, blood urea nitrogen, creatinine, and intact parathyroid hormone). Data expressed as the number of patients were analyzed by the c2 test. Variables that were significantly associated with arterial stiffness in the KT patients were tested for independence by multivariate logistic regression analysis. Data were analyzed using SPSS for Windows (version 13.0; SPSS Inc., Chicago, IL). P < .05 was considered significant.
RESULTS
Demographic, biochemical, and clinical characteristics of the 74 KT patients are presented in Table 1 and immunosuppressive drugs used are presented in Table 2. Comorbid conditions included diabetes (n ¼ 29; 39.2%), and hypertension (n ¼ 20; 27.0%). Prescribed therapeutic agents included tacrolimus (n ¼ 43; 58.1%), mycophenolate mofetil or mycophenolic acid (n ¼ 53; 71.6%), steroids (n ¼ 60; 81.1%), rapamycin (n ¼ 14; 18.9%), and cyclosporine (n ¼ 18; 24.3%). Diabetes (P < .001) and hypertension (P < .001) were more frequent in the high arterial stiffness group compared with the low arterial stiffness group (Fig 1). There were no significant differences by gender or transplantation model, use of tacrolimus, mycophenolate mofetil, mycophenolic acid, steroids, rapamycin, or cyclosporine in the high arterial stiffness group compared with the low arterial stiffness group. The clinical characteristics of the KT patients in high arterial stiffness group compared with low arterial stiffness group are presented in Table 3. Forty patients (54.1%) were defined in high arterial stiffness group. Age (P ¼ .010), KT duration (P ¼ .013), TG (P ¼ .016), SBP (P < .001), waist circumference (P ¼ .031), and leptin level (P < .001) were higher, while serum HDL-C level (P ¼ .030) was lower in
LEPTIN AND ARTERIAL STIFFNESS
355
Table 1. Clinical and Analytical Characteristics of 74 Renal Transplant Recipients Parameter
Anthropometric data Height (cm) Body weight (kg) Body mass index (kg/m2) Body fat mass (%) Left, baPWV (m/s) SBP (mm Hg) Waist circumference (cm) Age (y) KT duration (mo) Right, baPWV (m/s) DBP (mm Hg) Biochemical data WBC (1000/mL) Triglyceride (mg/dL) HDL-C (mg/dL) Fasting glucose (mg/dL) Blood urea nitrogen (mg/dL) Phosphorus (mg/dL) iPTH (pg/mL) Hemoglobin (g/dL) Total cholesterol (mg/dL) LDL-C (mg/dL) Creatinine (mg/dL) Total calcium (mg/dL) Ca IP product Leptin (ng/mL)
Table 2. Baseline Characteristics of the 74 Renal Transplant Recipients With or Without Arterial Stiffness
Mean SD Characteristic
162.16 62.61 27.74 29.12 13.98 139.05 85.12 52.07 72.19 14.23 86.18
8.33 12.59 4.21 6.40 2.52 16.57 11.41 9.63 42.99 2.68 10.88
6.99 162.24 51.34 110.38 28.69 3.42 149.22 12.73 195.79 108.79 1.99 9.19 30.99 42.11
2.38 159.46 15.93 45.33 20.76 0.86 164.79 5.29 45.84 38.97 1.74 1.04 6.62 34.02
baPWV, brachial-ankle pulse wave velocity; Ca IP product, calciume phosphorous product; DBP, diastolic blood pressure; HDL-C, high density lipoprotein cholesterol; iPTH, intact parathyroid hormone; KT, kidney transplantation; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; WBC, white blood count.
the high arterial stiffness group compared with the low arterial stiffness group (Fig 2). Multivariate logistic regression analysis of the factors significantly associated with arterial stiffness (diabetes, hypertension, age, KT duration, TG, SBP, waist circumference, HDL-C, and leptin) showed that leptin (odds ratio [OR], 1.033; 95% CI, 1.004e1.062; P ¼ .023), KT duration (OR, 1.023; 95% CI, 1.004e1.044; P ¼ .020), and HDL-C level (OR, 0.925; 95% CI, 0.872e0.982; P ¼ .010) were the independent predictors of peripheral arterial stiffness in KT patients (Table 4). DISCUSSION
The results of our study showed that high prevalence of peripheral arterial stiffness in KT patients. Fasting serum leptin level, KT duration, and HDL-C level were independent predictors of peripheral arterial stiffness among the KT patients. Arterial stiffness represents vascular damage and is a known independent predictor of cardiovascular mortality [16]. Cardiovascular disease is still a major cause of mortality in KT patients [1]. The annual risk of fatal or non-fatal cardiovascular events in KT recipients is 3.5% to 5%, which
Low Arterial Stiffness Group, n (%)
High arterial Stiffness group, n (%)
Gender Male 16 (47.1) 24 (60.0) Female 18 (52.9) 16 (40.0) Diabetes No 31 (91.2) 20 (50.0) Yes 3 (8.8) 20 (50.0) Hypertension No 32 (94.1) 22 (55.0) Yes 2 (5.9) 18 (45.0) Transplantation model Cadaveric 32 (94.1) 32 (80.0) Living 2 (5.9) 8 (20.0) Tacrolimus use No 12 (35.3) 19 (47.5) Yes 22 (64.7) 21 (52.5) Mycophenolate mofetil or mycophenolic acid use No 7 (20.6) 14 (35.0) Yes 27 (79.4) 26 (65.0) Steroid use No 5 (14.7) 9 (22.5) Yes 29 (85.3) 31 (77.5) Rapamycin use No 29 (85.3) 31 (77.5) Yes 5 (14.7) 9 (22.5) Cyclosporine use No 27 (79.4) 29 (72.5) Yes 7 (20.6) 11 (27.5)
P Value
.266
C
ARDIOVASCULAR DISEASE remains a major cause of mortality in kidney transplant (KT) patients, which is partially attributed to nonclassic cardiovascular risk factors, including arterial stiffness [1,2]. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in KT patients [3]. Pulse wave velocity (PWV) measurement is one of the noninvasive methods that are currently used to assess vascular dysfunction [4]. A close correlation between brachial-ankle PWV (baPWV) and carotid-femoral PWV has been reported [5]. Leptin is almost exclusively secreted by white and brown adipocytes [6]. Leptin plays a pathophysiologic role in the pathogenesis of hypertension and cardiovascular diseases [7]. Leptin may contribute to the development of arterial hypertension mainly through increased sympathetic nervous activity, and the development of endothelial dysfunction ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 353e358 (2014)
through the regulation of blood vessel tonus and imbalance between endothelial nitric oxide synthase expression and intracellular L-arginine [8,9]. Leptin may participate in the pathogenesis of atherogenesis through the stimulation of platelet aggregation, inflammation, endothelial dysfunction,
From the School of Medicine, Tzu Chi University (M.-C.L., B.G.H.), and the Departments of Surgery (M.-C.L., Y.-C.C., G.-J.H.), Nursing (M.-H.S., K.-C.C.), and Nephrology (B.-G.H.), Buddhist Tzu Chi General Hospital, Hualien, Taiwan. Supported by a grant from Buddhist Tzu Chi General Hospital, Hualien, Taiwan (TCRD101-06). Address reprint requests to Bang-Gee Hsu, Division of Nephrology, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Chung Yang Road, 97004 Hualien, Taiwan. E-mail: gee.lily@ msa.hinet.net 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.145 353
354
neointimal hyperplasia, neutrophil chemotaxis, and vascular smooth muscle cell proliferation and migration [7,10]. Leptin is independent correlates of carotid-femoral PWV in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging [11]. The aim of the present study was to determine the relationship between serum leptin concentrations and peripheral arterial stiffness among KT patients. PATIENTS AND METHODS Patients Seventy-four KT patients were studied in April 2010 in a medical center in Hualien, Taiwan, including 40 males and 34 females with ages ranging from 27 to 75 years. The study was approved by the Protection of Human Subjects Institutional Review Board of TzuChi University and Hospital. Patients were excluded if they had any acute infection, malignancy, acute rejection, acute myocardial infarction, pulmonary edema, heart failure at the time of blood sampling, an arterial-venous shunt or graft in the hands, or if they refused to provide informed consent for the study.
Anthropometric Analysis Body weight was measured to the nearest half kilogram with the patient in light clothing and without shoes. Height was measured to the nearest half centimeter, and waist circumference was measured to the nearest half centimeter at the shortest point below the lower rib margin and the iliac crest. Body mass index was calculated as weight (kilograms) divided by height squared (meters) [12e14].
Biochemical Determinations Fasting blood samples of approximately 5 m1 for measuring complete blood cell count (Sysmex K-1000, Sysmex, Bohemia, NY) and other factors were immediately centrifuged at 3000 g for 10 minutes after collection. Serum samples were stored at 4 C and used for biochemical analyses within 1 hour of collection. Serum levels of blood urea nitrogen, creatinine, fasting glucose, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol, total calcium, and phosphorus were measured using an autoanalyzer (COBAS Integra 800, Roche Diagnostics, Basel, Switzerland). Serum leptin (SPI-BIO, Montigny le Bretonneux, France) concentrations were determined using a commercially available enzyme immunoassay [12,13]. The minimum detectable concentration of human leptin dose was determined by adding 2 standard deviations to the mean optical density value of twenty zero standards replicates and calculating the corresponding concentration was 7.8 pg/mL. The inter- and intra-assay coefficients of variation for leptin were 4.2% and 3.0%. Serum intact parathyroid hormone (Diagnostic Systems Laboratories, Webster, TX) levels were measured using a commercially available enzyme-linked immunosorbent assays [12e14].
Blood Pressure and baPWV Measurements After blood sampling, baPWV measurements were taken the same day. Measurements were performed in a quiet, temperaturecontrolled room after 10 minutes at rest, with the patients in a supine position according to the recommendations for user procedures of clinical applications of arterial stiffness. Blood pressure and heart rate (mean of 3 readings) were measured with an automatic upper arm oscillometric device. Pulse pressure was calculated
LEE, CHEN, HO ET AL by subtracting diastolic (DBP) from systolic blood pressure (SBP). The baPWV was measured in the right or left brachial artery to the ankle segments using an automatic pulse wave analyzer (VaSera VS-1000, Fukuda Denshi Co. Ltd., Tokyo, Japan). In brief, cuffs were applied to the 4 extremities and electrocardiographic electrodes were attached to the upper arm. A microphone was placed on the sternal angle for phonocardiography. The subjects then rested in a supine position for 5 minutes. The baPWV was calculated by dividing the distance from the aortic valve to the ankle artery by the sum of the difference between the time the pulse waves were transmitted to the brachium and the time the same waves were transmitted to the ankle, and the time difference between the second heart sound on the phonocardiogram and the notch of the brachial pulse wave. To minimize cuff inflation effects on blood flow dynamics, pulse waves were measured with the cuffs inflated to less than the DBP (50 mmHg). The extremity blood pressure was then measured by oscillometry. SBP and DBP were obtained by measuring the blood pressure at the right brachial artery [15]. In this study, left or right baPWV values of less than 14.0 m/s were used to define the high arterial stiffness group [15].
Statistical Analysis Data were expressed as mean values standard deviation (SD) and were tested for normal distribution using the KolmogoroveSmirnov test. Comparisons between patients were performed using the Student’s independent t test (2-tailed) for normally distributed data, or the Mann-Whitney U test for parameters that presented with non-normal distribution (TG, fasting glucose, blood urea nitrogen, creatinine, and intact parathyroid hormone). Data expressed as the number of patients were analyzed by the c2 test. Variables that were significantly associated with arterial stiffness in the KT patients were tested for independence by multivariate logistic regression analysis. Data were analyzed using SPSS for Windows (version 13.0; SPSS Inc., Chicago, IL). P < .05 was considered significant.
RESULTS
Demographic, biochemical, and clinical characteristics of the 74 KT patients are presented in Table 1 and immunosuppressive drugs used are presented in Table 2. Comorbid conditions included diabetes (n ¼ 29; 39.2%), and hypertension (n ¼ 20; 27.0%). Prescribed therapeutic agents included tacrolimus (n ¼ 43; 58.1%), mycophenolate mofetil or mycophenolic acid (n ¼ 53; 71.6%), steroids (n ¼ 60; 81.1%), rapamycin (n ¼ 14; 18.9%), and cyclosporine (n ¼ 18; 24.3%). Diabetes (P < .001) and hypertension (P < .001) were more frequent in the high arterial stiffness group compared with the low arterial stiffness group (Fig 1). There were no significant differences by gender or transplantation model, use of tacrolimus, mycophenolate mofetil, mycophenolic acid, steroids, rapamycin, or cyclosporine in the high arterial stiffness group compared with the low arterial stiffness group. The clinical characteristics of the KT patients in high arterial stiffness group compared with low arterial stiffness group are presented in Table 3. Forty patients (54.1%) were defined in high arterial stiffness group. Age (P ¼ .010), KT duration (P ¼ .013), TG (P ¼ .016), SBP (P < .001), waist circumference (P ¼ .031), and leptin level (P < .001) were higher, while serum HDL-C level (P ¼ .030) was lower in
LEPTIN AND ARTERIAL STIFFNESS
355
Table 1. Clinical and Analytical Characteristics of 74 Renal Transplant Recipients Parameter
Anthropometric data Height (cm) Body weight (kg) Body mass index (kg/m2) Body fat mass (%) Left, baPWV (m/s) SBP (mm Hg) Waist circumference (cm) Age (y) KT duration (mo) Right, baPWV (m/s) DBP (mm Hg) Biochemical data WBC (1000/mL) Triglyceride (mg/dL) HDL-C (mg/dL) Fasting glucose (mg/dL) Blood urea nitrogen (mg/dL) Phosphorus (mg/dL) iPTH (pg/mL) Hemoglobin (g/dL) Total cholesterol (mg/dL) LDL-C (mg/dL) Creatinine (mg/dL) Total calcium (mg/dL) Ca IP product Leptin (ng/mL)
Table 2. Baseline Characteristics of the 74 Renal Transplant Recipients With or Without Arterial Stiffness
Mean SD Characteristic
162.16 62.61 27.74 29.12 13.98 139.05 85.12 52.07 72.19 14.23 86.18
8.33 12.59 4.21 6.40 2.52 16.57 11.41 9.63 42.99 2.68 10.88
6.99 162.24 51.34 110.38 28.69 3.42 149.22 12.73 195.79 108.79 1.99 9.19 30.99 42.11
2.38 159.46 15.93 45.33 20.76 0.86 164.79 5.29 45.84 38.97 1.74 1.04 6.62 34.02
baPWV, brachial-ankle pulse wave velocity; Ca IP product, calciume phosphorous product; DBP, diastolic blood pressure; HDL-C, high density lipoprotein cholesterol; iPTH, intact parathyroid hormone; KT, kidney transplantation; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; WBC, white blood count.
the high arterial stiffness group compared with the low arterial stiffness group (Fig 2). Multivariate logistic regression analysis of the factors significantly associated with arterial stiffness (diabetes, hypertension, age, KT duration, TG, SBP, waist circumference, HDL-C, and leptin) showed that leptin (odds ratio [OR], 1.033; 95% CI, 1.004e1.062; P ¼ .023), KT duration (OR, 1.023; 95% CI, 1.004e1.044; P ¼ .020), and HDL-C level (OR, 0.925; 95% CI, 0.872e0.982; P ¼ .010) were the independent predictors of peripheral arterial stiffness in KT patients (Table 4). DISCUSSION
The results of our study showed that high prevalence of peripheral arterial stiffness in KT patients. Fasting serum leptin level, KT duration, and HDL-C level were independent predictors of peripheral arterial stiffness among the KT patients. Arterial stiffness represents vascular damage and is a known independent predictor of cardiovascular mortality [16]. Cardiovascular disease is still a major cause of mortality in KT patients [1]. The annual risk of fatal or non-fatal cardiovascular events in KT recipients is 3.5% to 5%, which
Low Arterial Stiffness Group, n (%)
High arterial Stiffness group, n (%)
Gender Male 16 (47.1) 24 (60.0) Female 18 (52.9) 16 (40.0) Diabetes No 31 (91.2) 20 (50.0) Yes 3 (8.8) 20 (50.0) Hypertension No 32 (94.1) 22 (55.0) Yes 2 (5.9) 18 (45.0) Transplantation model Cadaveric 32 (94.1) 32 (80.0) Living 2 (5.9) 8 (20.0) Tacrolimus use No 12 (35.3) 19 (47.5) Yes 22 (64.7) 21 (52.5) Mycophenolate mofetil or mycophenolic acid use No 7 (20.6) 14 (35.0) Yes 27 (79.4) 26 (65.0) Steroid use No 5 (14.7) 9 (22.5) Yes 29 (85.3) 31 (77.5) Rapamycin use No 29 (85.3) 31 (77.5) Yes 5 (14.7) 9 (22.5) Cyclosporine use No 27 (79.4) 29 (72.5) Yes 7 (20.6) 11 (27.5)
P Value
.266
